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放射性粒子125I对胶质瘤细胞治疗作用的实验研究
潘宝根1,赵文清1,2*,李文玲2,王跃红1,边艳珠3
0
(1.河北医科大学外科教研室,石家庄 050031;2.河北省人民医院神经外科,石家庄 050051;3.河北省人民医院核医学科,石家庄 050051)
摘要:
目的探讨放射性粒子125I在动物体内抗人脑胶质瘤的效果及其作用机制。方法建立人胶质瘤的动物模型,瘤内植入放射性粒子125I,观察肿瘤生长情况,在电镜下观察其超微结构的变化,采用TUNEL技术检测肿瘤组织的凋亡情况,流式细胞仪检测Bax/Bcl-2的表达,并应用免疫组化染色检测血管密度和VEGF、bFGF的表达。结果成功建立了人胶质瘤细胞U251的动物模型,植入放射性粒子125I后,胶质瘤生长较对照组明显受到抑制(P<0.05,P<0.01),电镜下可呈现核断裂、染色质边聚等细胞凋亡的形态特征。检测显示:和对照组相比, 肿瘤组织的Bax/Bcl-2(1.88±0.47 vs 1.11±0.52,P<0.01)和组织凋亡率的IHS评分(3.64±0.89 vs 0.81±0.45,P<0.01)明显增高;肿瘤组织的微血管密度IHS评分(1.40±0.55 vs 3.23±0.87,P<0.01)、VEGF的IHS评分(1.58±0.55 vs 4.19±0.45,P<0.01)和bFGF的IHS评分(2.44±0.89 vs 3.52±0.79,P<0.05)明显降低。结论放射性粒子125I对在体人胶质瘤U251有明确的抑制作用,促进瘤细胞凋亡和降低瘤组织微血管密度可能是其主要作用机制。
关键词:  胶质瘤  间质内放疗  放射性核素125I  动物模型  细胞凋亡  微血管密度
DOI:10.3724/SP.J.1008.2010.046
投稿时间:2008-09-17修订日期:2009-12-06
基金项目:河北省自然科学基金(C2004000671).
Therapeutic effect of 125 I in treatment of nude mice implanted with human glioma
PAN Bao-gen1,ZHAO Wen-qing1,2*,LI Wen-ling2,WANG Yue-hong1,BIAN Yan-zhu3
(1.Department of Surgery,Hebei Medical University,Shijiazhuang 050031,Hebei,China;2.Department of Neurosurgery,Hebei General Hospital,Shijiazhuang 050051,Hebei,China;3.Department of Nuclear Medicine,Hebei General Hospital,Shijiazhuang 050051,Hebei,China)
Abstract:
ObjectiveTo investigate the efficacy of 125 I in treatment of nude mice implanted with human glioma cell line U251 and the related mechanism.MethodsThe animal models of human malignant glioma were established with nude mice.125 I was implanted into tumors and the tumor growth was observed.The ultrastructural change was observed by electron microscopy.The apoptosis of the tumor tissue was examined by in situ end-labelling technique; expression of Bax/Bcl-2 was detected by flow cytometer.Blood vessel density and expression of VEGF,bFGF were observed by immunohistochemistry.ResultsNude mouse models of human malignant glioma were successfully established.Compared with control group,125 I significantly inhibited tumor growth in nude mice(P<0.05,P<0.01).Electron microscopy demonstrated that the tumor cells displayed apoptosis characteristics such as nuclear fragmentation,margination of condensed chromatin.The expression of Bax/Bcl-2 in the 125I implanting group (1.88±0.47)was significantly increased compared with that in the control group (1.11±0.52,P<0.01),and the apoptosis rate of tumor tissues in the 125I implanting group (3.64±0.89) was significantly higher(0.81±0.45,P<0.01).The blood vessel density in the 125I implanting group was significantly lower than that in the control group (1.40±0.55 vs 3.23±0.87,P<0.01).The expression of VEGF,bFGF in 125I implanting group was significantly lower than that in the control group (1.58±0.55 vs 4.19±0.45 for VEGF,P<0.01; 2.44±0.89 vs 3.52±0.79 for bFGF,P<0.05).Conclusion125I has prominent inhibitory effect against human gliomas,and the main mechanism might be the promotion of apoptosis and decrease of blood vessel density.
Key words:  glioma  brachytherapy  radioisotope 125I  animal model  apoptosis  microvessel density